The subject matter discussed in the background section should not be assumed to be prior art merely as a result of its mention in the background section. Similarly, a problem mentioned in the background section or associated with the subject matter of the background section should not be assumed to have been previously recognized in the prior art. The subject matter in the background section merely represents different approaches, which in and of themselves may also be inventions.
Quantitative assessment of body tissues and organs from CT (computed tomography) scans represents an important element in many different areas of medicine, for example, in measuring such parameters as bone density or strength at the hip or spine, mineral content in blood vessels, hepatic-fat content in the liver, and gray-to-white matter ratio in the brain. Such quantitative assessments are based in part on some type of quantitative analysis of the X-ray attenuation gray-scale values—commonly referred to as the “CT-numbers”—in the CT scan. The CT-number is usually reported as a Hounsfield Unit (HU), which is a linear scale of X-ray attenuation in which the attenuation of water and air are defined as 0 HU and −1000 HU, respectively. However, calibration of the HU-values or any other type of CT-number is required to correct for inevitable variations in scanner characteristics, beam-hardening, and patient characteristics, any of which can alter the CT-numbers. Without such calibration, for example, the same patient would yield different CT-numbers if imaged on different CT machines or with different scanner settings, confounding the interpretation and clinical utility of the quantitative assessment. When CT scans are calibrated for quantitative assessment, this is commonly referred to as “quantitative CT”. The current invention provides improved means of calibration of a CT scan, such improvement facilitating the use of quantitative CT clinically.
The most widely used prior art method of calibration for quantitative CT, used primarily for measurement of bone mineral density, requires the use of some type of external calibration phantom. However, the need for an external calibration phantom, which must be placed under the patient during scanning, adds expense and complexity to the clinical imaging and is therefore not widely used. Another limitation of using an external calibration phantom is that the outcome measures of calibrated density of a tissue are always expressed in terms of the density or concentration of the materials used in the actual phantom; such measures of density are referred to as “equivalent-density” measures. This means that the same tissue for a patient, if measured using different types of external calibration phantoms, may be assigned different values of equivalent-density. This makes clinical interpretation difficult, which hampers widespread clinical adoption of the quantitative CT technology.
To circumvent the need for an external calibration phantom while imaging patients, methods have been developed in which a “pre-calibration” of a particular CT machine is first characterized, typically in some type of research setting using an external calibration phantom, and then that pre-calibration characterization is used clinically for patients without the subsequent need for the external calibration phantom. However, while this method can account for between-machine differences in calibration characteristics for any particular CT machines that are pre-calibrated, it does not account for any patient-specific X-ray attenuation characteristics and thus does not provide a patient-specific calibration; nor it is applicable to CT machines that have not been pre-calibrated or to pre-calibrated CT machines with hardware components that deteriorate over time. A patient-specific phantomless calibration method has been developed in an attempt to address these limitations (U.S. Pat. No. 5,068,788), this method utilizing muscle and fat inside the body as calibration-reference materials. However, since muscle is mixed with fat—and since the ratio of pure fat to pure muscle tissue varies both across patients and within the body—it is difficult to separate out the fat and muscle in a repeatable and reliable fashion. As noted by Pickhardt (2011), these limitations present barriers to clinical use. Combining some aspects of both external-phantom calibration and phantomless calibration, a “hybrid” calibration approach has also been developed (U.S. Pat. Nos. 6,990,222 and 7,292,721). In this approach, an external calibration phantom is used in conjunction with internal body tissues to provide a refinement on the calibration obtained from the external calibration phantom. However, this technique is limited since it also requires the use of an external calibration phantom either before or during imaging the patient.
For certain applications, for example, when measuring bone mineral density, it would also be desirable to be able to use a phantomless calibration technique on CT scans that were acquired using an intravenous contrast agent. Performing a phantomless calibration of such contrast-enhanced CT scans is confounded by the intravenous contrast agent, which is a radio-opaque material injected into the blood. This contrast agent alters the appearance of the blood and (highly perfused) muscle in the CT scan, so these tissues cannot be used as internal reference tissues.
Thus, despite the availability of a number of different approaches to calibrating clinical CT scans with or without an external calibration phantom for use in quantitative CT, there remains a need for a phantomless calibration method that does not require the use of an external calibration phantom, that accounts for machine-specific and patient-specific differences in X-ray attenuation characteristics within the body, that is precise and repeatable, that can be used retrospectively on previously acquired CT scans, and that can sometimes be used in contrast-enhanced scans.
Such a phantomless calibration technique would have widespread clinical utility since it would facilitate implementation of a variety of prior-art quantitative CT applications for which a calibration of the CT scan is desired, but which currently is performed either using no calibration—which has questionable validity as a clinical test—or using one of the prior-art methods of calibration, all of which have their own limitations as noted above. Bone applications include osteoporosis and orthopaedic surgical planning, in which measurements of bone density, bone strength, bone geometry, or bone-implant strength are taken for a specific patient utilizing a patient's CT scan. Non-bone applications include any quantitative assessment of fat or mineral content in soft tissues, a fat-to-liver ratio in the liver in patients with fatty liver disease, measurement of mineral content in blood vessels for cardiovascular assessment, and assessment of the gray-to-white matter ratio in the brains of patients after stroke or cardiac arrest. In addition to these quantitative CT applications, displaying consistent gray-scale values in the CT scan across different CT machines and scanner settings via use of an automated phantomless calibration method can also enhance viewing and qualitative interpretation of CT images.